Adverse physiological and neuromuscular response to laryngoscopy and intubation remains a significant problem of airway manipulation, both during anaesthesia and other airway diagnostic procedures. This is more fully discussed in the above-identified pending application the substance of which is incorporated hereby by reference thereto.
There is a need for an improved method of delivering a topical anaesthetic to a patient's airway and this is partly addressed by the aforementioned application. There further is need of a topical anaesthetic in suitable form for delivery into a patient's airway.
A known recommended procedure for airway anaesthetic administration is set forth in a text entitled "Clinical Anaesthesia" second edition edited by Paul G. Barash M.D. et al and published by J.B. Lippincott Company.
In this text it is indicated that "In airway anaesthesia manipulation of the airway either during laryngoscopy or during endotracheal intubation is often associated with laryngospasm, coughing, and undesirable cardiovascular reflexes. The anesthesiologist can abolish or blunt these reflexes by anaesthetizing one or all of the sensory pathways involved.
Airway anaesthesia can be performed by anaesthetizing one or all of the number of sensory distributions. Full anaesthesia will facilitate procedures such as nasal intubation or fiberoptic laryngoscopy.".
The procedure for airway anaesthetic administration described in the aforementioned text includes:
(1) nasal mucosal anaesthesia in which cotton pledgets soaked with anaesthetic solution are introduced through the nares. Contact time of "at least 2-3 minutes is required to allow adequate diffusion of the anaesthetic" which traditionally is "cocaine in a 4% solution". "Because of toxicity of cocaine and" "abuse problems" "alternate solutions have been recommended--primarily a mixture of 3-4% lidocaine and 0.25-0.5% phenylephrine". PA1 (2) Topical anaesthesia to the posterior pharynx using a commercial spray while the nasal applicators are in place. It is indicated that "The inspiratory flow of gases should be enough to draw an anaesthetic solution into the posterior pharynx and even to the vocal cords themselves. If superior laryngeal nerve blockade has been performed prior to this, it is likely that the aerosol will be carried into the trachea itself. Again, a few minutes are needed for adequate onset of topical anaesthesia in the pharynx. Topical anaesthesia is less effective if there are copious secretions.". PA1 (3) "Superior laryngeal nerve blockade, also performed while the nasal pledgets are in place", using a "5-ml syringe with a 1% lidocaine solution with a 23 gauge 1.75-cm needle". The aforementioned text indicates "blockade can be performed as part of total airway anaesthesia or it can be used independently to provide increased acceptance of indwelling endotracheal tubes in the intensive care unit". PA1 (4) "Tracheal anaesthesia can be performed by a direct transcrycoid ("transtracheal") injection". The aforementioned text indicates "Not uncommonly, if the local anaesthetic is injected while the patient forcibly exhales it is possible to obtain adequate anaesthetic of the trachea, larynx, and posterior pharynx, without the need for either steps 2 or 3.". PA1 (5) Lidocaine can be nebulized using a nebulizer driven by oxygen flow or airflow. The mist is breathed by the patient through an oxygen mask for 10-20 minutes. This will non-invasively topicalize the upper airway but is time consuming and requires patient co-operation. PA1 an aerosol-dispensable topical anaesthetic composition under pressure in a metered dosage-dispensing container; such PA1 an aerosol-dispensable topical anaesthetic composition wherein the lidocaine free base aerosol droplet particle size is 5 to 10 microns; such PA1 an aerosol-dispensable composition containing no solvent other than propellant; such PA1 an aerosol-dispensable anaesthetic wherein a metered dosage dispensed by the metered dosage-dispensing container is in the range of 5 to 20 mg of lidocaine free base per dose; such PA1 an aerosol-dispensable anaesthetic composition wherein the concentration of the lidocaine free base is greater than 3% by weight of the composition; such PA1 an aerosol-dispensable anaesthetic composition wherein the concentration of the lidocaine free base is greater than 5% by weight of the composition; such PA1 an aerosol-dispensable anaesthetic composition wherein the concentration of the lidocaine free base is approximately 5-15% by weight; such PA1 an aerosol-dispensable anaesthetic composition wherein said concentration is greater than 10 mg/ml and up to about 759 mg/ml; such PA1 an aerosol-dispensable anaesthetic wherein a metered dose dispensed by the metered-dose-dispensing container is up to about 100 microliters; such PA1 an aerosol anaesthetic wherein the concentration of the lidocaine free base provides at least 5 mg of lidocaine free base per metered dosage; such PA1 an aerosol-dispensable anaesthetic composition wherein the concentration of the lidocaine free base provides 5-20 mg of lidocaine free base per metered dosage; such PA1 an inhalation aerosol-dispensable topical anaesthetic composition in aerosol form consisting essentially of lidocaine free base of the formula C.sub.4 H.sub.22 N.sub.2 O dissolved in propellant CF.sub.3 CH.sub.2 F or CF.sub.3 CHFCF.sub.3, or a combination thereof, under pressure in a metered-dosage dispenser, the percentage of lidocaine free base by weight of the composition being at least 5 % and the lidocaine free base aerosol droplets having a particle size between 5 and 25 microns; such PA1 an inhalation aerosol-dispensable topical anaesthetic composition wherein the percentage of lidocaine free base by weight of the composition is 5 to 15%; and such PA1 an aerosol-dispensable topical anaesthetic composition wherein the lidocaine free base aerosol droplet particle size is 5 to 10 microns.
The authors say that "Complications of these techniques are rare. Systemic toxicity from the local anesthetics is a distinct possibility because of the large quantities of drug required to produce sufficient mucosal anaesthesia". There is a caution that "if all four stages of airway anaesthesia are undertaken, the total milligram doses applied usually exceed the maximal recommended dose for peripheral injection. Fortunately, the mucosal absorption is less than the peripheral absorption, but close attention to the patient's mental status and preparation of treatment of toxicity are necessary.".
The techniques described in this text are used to facilitate manipulation of the airway of an awake patient. These procedures require considerable skill, patient co-operation and time to achieve the desired result. Because of these factors airway topicalization is routinely reserved for airway manipulations involving awake or lightly sedated patients. Topical airway anaesthetic would be beneficial in all anesthetized patients where intubation or airway manipulation is done. This, however, is not practical. Anaesthetic drugs including muscle relaxants are used to achieve the desired result. Topical lidocaine applied through the endotracheal tube of an intubated and ventilated patient will blunt the response to tracheal suctioning. This procedure is performed routinely and often hourly in these patients to clear airway secretions.
A topical lidocaine aerosol is currently available from Astra Canada and known as "Xylocaine Endotracheal Aerosol" but it requires direct application under vision, best achieved at laryngoscopy. The laryngoscopy is disadvantageously performed without prior airway topical anaesthesia. Intubation carried out at the time of laryngoscopy occurs too soon after the anaesthetic agent is applied for significant benefit to be achieved.
The known lidocaine aerosol has been implicated in inducing transient airway irritation and even laryngospasm. This preparation of lidocaine uses chlorofluorocarbon (CFC) propellants which are being discontinued to meet legal requirements.
For a topical anaesthetic to be effective, delivery direct to the site is required. The large droplet size produced by the aforementioned known Xylocaine Aerosol and the more basic spray delivery method necessitate direct application to the desired site. Drug delivery to the airway and lung can be achieved indirectly by the patient inspiring the aerosol if the droplet size is small enough. Large drops have a tendency to "rain out" or impact on surfaces, rather than follow gas flow around an obstructing surface. Therefore, delivery will be largely to the patient's nasal and oral mucus membranes. Particle size is an important factor in therapeutic aerosols and this along with other considerations are discussed in a text entitled "Pharmaceutical Inhalation Aerosol Technology" edited by A. J. Hickey and published by Marcel Dekker. On page 31 of this text, particle size is correlated with destination site. An aerosol particle diameter .gtoreq.10 .mu.m targets a deposition site of the oropharynx and &gt;5.mu.m the central airways.
In the art of aerosols, surfactants normally are used to ensure good dispersion of a powdered medicant and also provide for smooth operation of the valve through which the composition is dispensed. Conventional surfactants are sorbitan triolate and oleic acid. Solvents have also been used to increase the solubility of the surfactant in the propellant. CFC's have been conventionally used as propellants but these are gradually to be replaced by propellants that are more environmentally friendly. There are proposals for using HFC propellants, and in this regard reference may be made to PCT/GB91/01961 International Publication WO92/08447 dated May 29, 1992; PCT/US91/07574 International Publication WO92/06675 dated Apr. 30, 1992 and PCT/GB90/01454 International Publication WO91/04011 published Apr. 4, 1991. In these disclosures surfactants are required.